Negative correlation between the Bern score and opening pressure in myelography positive spontaneous intracranial hypotension

Abstract Objective The Bern score is based on brain magnetic resonance imaging (MRI) to predict the probability of cerebrospinal fluid (CSF) leak in spontaneous intracranial hypotension (SIH). The aim of this study is to investigate the association between lumbar puncture opening pressure (OP) and the Bern score. Methods We retrospectively reviewed OP measurement records and neuroimaging of patients with SIH in our center. The Bern score and its components were measured based on contrast‐enhanced brain MRI. The associations between OP and the Bern score, as well as its components, were analyzed. Patients were divided as low‐pressure (LP) group (OP < 60 mmH2O) and not‐low‐pressure (NLP) group (OP ≥ 60 mmH2O). Differences in terms of the Bern score and its components were compared between the two groups. Results Seventy‐one (mean age 40.4 ± 10.6 years) patients with myelography confirmed CSF leak were included in this study. The mean disease duration when performed brain MRI was 32 ± 29 days, with a mean Bern score of 5.1 ± 2.7 and a mean OP of 68.6 ± 60.3 mmH2O. There are statistically negative correlations between OP and the Bern score (p < .001), as well as suprasellar cistern (p < .01) and prepontine cistern (p < .01). The presence of venous engorgement (p < .01) and pachymeningeal enhancement (p < .001) were significantly associated with OP. The LP groups have higher Bern scores than the NLP group (5.9 ± 2.5 vs. 4.2 ± 2.6, p = .004). Conclusions A higher Bern score is indicative of not only an increased likelihood of a CSF leak but also a greater probability of low OP in patients with SIH. For patients with a Bern score ≥5 and positive heavily T2‐weighted MR myelography findings, epidural blood patch is reasonable before invasive myelography.

In this setting, different tools are evolving to facilitate its diagnosis and detecting of CSF leak.The Bern score is a simple and easy-touse probabilistic scoring system based on brain magnetic resonance imaging (MRI) to predict the probability of CSF leak in SIH (Dobrocky et al., 2019).The score system ranges from 0 to 9, where 0 indicates a low probability of spinal CSF leak and 9 indicates a high probability.
In this study, we sought to investigate the association between lumbar puncture opening pressure (OP) and the Bern score, as well as with its components.The differences between patients with low OP and patients with normal or elevated OP in terms of the Bern score and its components were also compared.

Study population
Between

The Bern score
We applied the Bern score defined by Dobrocky, et al. (2019)  and mamillopontine distance (≤6.5 mm) (Dobrocky, et al., 2019).As defined by Dobrocky et al. (2019), patients with a Bern score of ≤2, 3-4, or ≥5 have a low, intermediate, or high probability of spinal CSF leak, respectively.Some scholars proposed a restricted Bern score in which the presence or absence of pachymeningeal enhancement was excluded from the scoring criteria (Callen et al., 2023).We also investigate the association between OP and restricted Bern score in this study.In patients for whom multiple brain MRIs were available in our center, the one with shortest time interval between lumbar puncture was adopted.

Heavily T2-weighted MRM
Heavily T2-weighted myelography was performed with a phase-array spine coil on a 1.5-T superconducting system (UIH µMR560).Axial MRMs were acquired at three levels (cervicothoracic, thoracic, and thoracolumbar), which overlapped at the margins, with the following parameters: repetition time 6000 ms, echo time 418 ms, matrix size 320 × 192, filed of view 224 × 224 mm, and slice thickness 6 mm.Postacquisition multiplanar reformation was performed to obtain axial (slice thickness 2 mm, gap 2 mm) and coronal images (slice thickness 2 mm, gap 2 mm).

Computed tomographic myelography (CTM)
A lumbar puncture through the L 3-4 or L 4-5 spinal interspace was performed in left lateral decubitus position with a 25-ga spinal needle.
After OP measurement, diluted nonionic iodinated contrast material (10 mL Iohexol, GE medical system, prediluted with 10 mL sterile 0.9% to lower lumbar spine was obtained about half an hour after contrast injection.The images were reconstructed into axial planes (slice thickness 1.5 mm), sagittal planes (slice thickness 1.5 mm), and coronal planes (slice thickness 1 mm).

Image analysis
All radiological imaging was reviewed by at least one board-certified neuroradiologist and one board-certified neurologist.When a disagreement between readers in any signs was identified, the finding was reviewed together to reach consensus (flowchart see Figure 1).

Statistical analysis
Descriptive analysis used frequencies and percentages for categorical variables and mean ± SD for continuous variables.Univariable regression models were used to evaluate the correlation between OP and the Bern score or its components.Spearman correlation analysis was used for continuous variables, whereas Kendall correlation analysis was used for categorical variables.According to the OP, we also divided patients as low-pressure (LP) group (<60 mmH2O) and notlow-pressure (NLP) group (≥60 mmH2O).Nonparametric analyses and Fisher's exact tests were used to compare categorical and continuous variables, respectively, between the two groups.

RESULTS
The final study cohort included 71 SIH patients with myelography confirmed CSF leak (LP: 37 patients and NLP: 34 patients; Table 1).Mean  2 and Figure 3).The presence of venous engorgement (p < .01)and pachymeningeal enhancement (p < .001) were significantly associated with OP (Table 2).A negative correlation was also found between OP and the restricted Bern score (p = .002) (Table 2 and Figure 3).
The Bern scores are larger in the LP group than those in the NLP group (5.9 ± 2.5 vs. 4.2 ± 2.6, p = .004).It is similar for restricted Bern score (LP 4.6 ± 2.0 vs. NLP 3.5 ± 2.0, p = .025)(Table 1).Correspondingly, there are also differences in the Bern score distributions between the two groups (p = .025)(Figure 4).In terms of different components of the Bern score, the percentage of patients with pachymeningeal enhancement (67.6% vs. 32.4%,p = .004)was higher in the LP group (Table 1).The height of suprasellar cistern (3.3 ± 2.2 mm vs. 4.6 ± 3.1 mm, p = .044)was shorter in the LP group (Table 1).

DISCUSSION
In this retrospective study, we found a statistically negative correlation between the Bern score and OP in patients with myelography con-  OP should not be used to exclude patients from further diagnostic process when there is clinical suspicion for SIH (Callen et al., 2023).
Based on different etiology, morphology, and distance from the midline, CSF leak was classified into four types by scholars (Schievink et al., 2016;Farb et al., 2019).Type 1 is caused by degenerative disc disease creating a mechanical tear in the ventral dura.Type 2 leaks due to a more lateral tear near neural foramina, usually combined with meningeal diverticula.Type 3 is caused by a direct CSF-venous fistulas.However, type 4 results from a distal nerve root sleeve leak into the adjacent facial planes (Farb et al., 2019).
In clinical practice, brain MRI is usually done first in patients presenting with new onset headaches.To standardize the diagnostic pathways of patients with SIH, Dobrocky et al. (2019) proposed this 3tier predictive scoring system (the Bern score), which is based on the six most relevant brain MRI findings.Patients with a Bern score of ≤2, 3-4, or ≥5 have a low, intermediate, or high probability of spinal CSF leak, respectively (Dobrocky et al., 2019).Although in the cohort developing the Bern score, SIH patients caused by CSF-venous fistula were not included (Dobrocky et al., 2019), recent studies indicate that the Bern score could also predict CSF-venous fistula (Callen et al., 2023;Kim et al., 2021).A recent study shows that the Bern score could also serve as a reliable quantitative tool to monitor treatment success in SIH patients (Dobrocky et al., 2022).
Suggested by Dobrocky et al. (2019), for patients with a Bern score ≥5, considering the high probability of positive findings in myelography, EBP should be considered promptly without performing myelography.
In our study, the mean Bern score is above 5.Besides, the Bern score of LP group was larger than 5, whereas that of the NLP group is smaller than 5. Based on our clinical practice as well as suggested by literature, for patients with OP < 60 mmH 2 O, the likelihood of contrast injection failure (extrathecal contrast injection) is high due to changes in spinal membrane elasticity during myelography (Beck et al., 2017;Xu et al., 2018).Therefore, our study also supports the recommendation that for patients with a Bern score ≥5 and positive heavily T2-weighted MRM findings, targeted EBP is reasonable before an invasive myelography.
Although our study did not included CSF-venous fistula patients, considering this type of CSF leak is usually negative in MRM and refractory to EBP, this recommendation also has its rationality.reduced prepontine and mamillopontine distance (Chen et al., 2022).
In our study, we find venous engorgement; pachymeningeal enhance-  (Beck et al., 2017;Callen et al., 2023;Kranz et al., 2016).OP may be determined in a more complex manner than has been generally understood.Future work is needed to address these questions.
Among the five typical neuroimaging findings in the brain MR enhanced with contrast (known as SEEPS), the occurrence of pachymeningeal enhancement is highest, with an incidence of approximately 80% (Dobrocky et al., 2019;Kranz, et al., 2016) et al., 2022).Fourth, our study is retrospective and monocentric with modest sample size.
Although previous study showed that a higher Bern score is not necessarily indicative of more severe cases of SIH (Dobrocky et al., 2019).
The onset-neuroimaging interval is also suggested to be considered when using brain MRI finding score system for diagnostic purposes (Chen et al., 2022).But all in all, our study supports that a Bern score ≥5 is of important diagnostic and guiding management value in patients with SIH in Chinese population.

CONCLUSION
The Bern score is also a simple and easy-to-use diagnostic tool to predict the probability of CSF leak in Chinese population.A higher Bern score is indicative of not only an increased likelihood of a CSF leak but also a greater probability of low OP.For patients with a Bern score ≥5, promptly EBP based on brain MRI and heavily T2-weighted MR myelography is reasonable before invasive evaluations.
January 1, 2019 and December 31, 2021, 720 patients with a clinical suspicion of SIH underwent clinical work-up at Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University.The inclusion criteria of this study included: (1) patients met diagnostic criteria for SIH according to the third edition of the International Classification of Headache Disorders (ICHD-3); (2) patients with adequate baseline brain contrast-enhanced MRI performed prior to first ever epidural blood patch (EBP) or CSF leak surgery; (3) patients with lumbar puncture OP measurement record in our center.It should be noted that in our center lumbar puncture is performed for myelography, not just for measurement of OP; (4) CSF leak was confirmed by heavily T2weighted magnetic resonance myelography (MRM) and/or computed tomographic myelography (CTM).SIH caused by CSF-venous fistula may demonstrate negative result in MRM or CTM, digital subtraction myelography (DSM) is required in these patients to localize CSF leak.Because our center has not yet conducted DSM, so CSF-venous fistula patients were not included in this study.The exclusion criteria included: (1) secondary intracranial hypotension, for instance, post-dural puncture headache; (2) symptoms of intracranial hypotension relieved upon admission; (3) unclear diagnosis of intracranial hypotension or with no proven CSF leak; (4) inadequate brain MRI (without contrast-enhanced brain MRI, MRI with artifact resulting in the inability to evaluate the Bern score, or MRI acquired >2 weeks time interval between lumbar puncture); (5) age younger than 18 years.Retrospectively, we reviewed medical records and neuroimaging of patients included.This study was approved by the Institutional Review Board Committee (Project ID 20210729-075), which waived the requirement of written informed consent due to the retrospective study design.
originally published on JAMA Neurology 2019, which integrates six imaging findings in brain MRI: three major (two points each), engorgement of venous sinus, pachymeningeal enhancement, and effacement of the suprasellar cistern (≤4.0 mm) and three minor (one point each), subdural fluid collection, effacement of the prepontine cistern (≤5.0 mm), saline) was slowly injected around 10 min.The patient was then placed in the supine, right, prone, and left position in sequences, changing positions every 5 min, with a pillow under the buttocks.The patient was transferred at the same time to prepare for a CT scan.Helical CT (Siemens SOMATOM Definition Flash) scan from upper cervical F I G U R E 1 Study flowchart.Cerebrospinal fluid (CSF) cerebrospinal fluid, magnetic resonance imaging (MRI) magnetic resonance imaging, and spontaneous intracranial hypotension (SIH) spontaneous intracranial hypotension.* inadequate brain MRI stands for brain MRI without contrast-enhanced, MRI with artifacts resulting in the inability to evaluate the Bern score, or MRI acquired >2 weeks time interval between lumbar puncture.

F
Figure 2.There are statistically negative correlations between OP and the Bern score (p < .001),as well as suprasellar cistern (p < .01)and prepontine cistern (p < .01)(Table2and Figure3).The presence of venous firmed SIH.Patients with low OP overall have larger Bern scores than patients with normal or elevated pressure.According to ICHD-3, either an OP < 60 mmH 2 O on lumbar puncture or typical neuroimaging findings of intracranial hypotension (either direct on spine imaging or indirect on brain imaging) are required for a diagnosis of SIH (Callen et al., 2023; ICHD-3, 2018).However, contrary to what its name might suggest, about half of the F I G U R E 3 Correlation between opening pressure and the Bern score (a), as well as two continuous variables (b and c) of its six components.Correlation between opening pressure and the restricted Bern score (d).F I G U R E 4 The distributions of Bern score in low-pressure (LP) group and not-low-pressure (NLP) group (p = .025).The Bern score ranges from 0 to 9. Patients with a score of 0-2 have a low, 3-4 an intermediate, and 5-9, a high probability of spinal cerebrospinal fluid (CSF) leak.
Callen et al. (2023) illustrated the average Bern score in individuals with a CSF leak was significantly higher than in those without.In our study, we reported a statistically negative correlation between the Bern score and OP in patients with invasive myelography confirmed SIH.The Bern score contains two main pathophysiologic variables in SIH: (1) those relating to increased intracranial vascular volume replacing loss of CSF, including venous engorgement, pachymeningeal enhancement, and subdural fluid collection and (2) those structural changes reflecting brain sagging due to reduced buoyancy, including Patients with opening pressure record and myelography confirmed CSF leak.
TA B L E 1Note: All the brain MRIs wereYao & Hu, 2017)re first-ever epidural blood patch or CSF leak surgery.The time intervals between brain MRI scanning and lumbar puncture were within 2 weeks.The Bern score ranges from 0 to 9, with 0 indicating very low and 9 very high probability of spinal CSF leak.Data are number (%) or mean (SD).Nonparametric analyses were used for continuous variables.Fisher's exact tests were used for categorical variables.Abbreviations: CSF, cerebrospinal fluid; MRI, magnetic resonance imaging; SD, standard deviation.aSpearmancorrelationanalysis.bKendallcorrelation analysis.patientswithCT myelography confirmed CSF leak have normal or even elevated lumbar puncture OP, as shown in previous studies(Kranz, Tan-  pitukpongse et al., 2016;Yao & Hu, 2017).Therefore, OP < 60 mmH 2 O is not a necessary condition for diagnosing SIH.Of importance in turn, , non-contrasted, and time-saving method for assessing the location of CSF leak.Scholars have compared these two different ways of myelography, which indicates that heavily T2-weighted MRM , especially as low OP is an unreliable marker.Various imaging tools are used to diagnose and localize CSF leak.Currently, dynamic myelography is required to localize a CSF leak precisely, but this is invasive, time-consuming, costly, and ionizing radiative.Besides, it may also expose the patient to complications, especially for those patients who already have subdural hematomas.Besides invasive myelography, heavily T2-weighted MRM is a noninvasive (Chen et al., 2022)Mokri, 1999) prepontine distance are associated with OP.When comparing patients with low OP and not-low OP, pachymeningeal enhancement and suprasellar cistern were different between the two groups.Previous studies illustrate that there is no difference between LP and NLP SIH in terms of symptoms, neuroimaging, and response to treatment, except that the NLP group have longer disease duration(Chen et al., 2022;Mokri, 1999).Shun-Jiun Wang et al. found that cerebral venous dilation-related brain MRI findings generally developed earlier than brain deformity-related brain MRI findings(Chen et al., 2022).Therefore, the difference between low OP and not-low OP patients may lie primarily in different dominant compensation mechanisms.Patients with low OP may have more obvious venous dilation due to the low intracranial pressure, which consists of the Monro-Kellie postulate.While in patients with normal or ele- Our study has several limitations.First, referral bias may exist as our center is the largest center for SIH management in China mainland.Many of our patients were transferred from other provinces and had unsuccessful initial treatment at local hospitals.Second, lumbar puncture was not routinely performed in all the patients with a suspicion of SIH in our center.For patients with typical symptoms, typical brain MRI and heavily T2-weighted MRM, or patients with severe complications, such as subdural hematoma or cerebral venous thrombosis, conventional myelography was not performed.Therefore, according to our research purpose, inclusion and exclusion criteria, some clinical characteristics of patients in our cohort may not represent the overall characteristics of SIH patients.For example, the mean Bern score in our cohort does not represent the overall mean Bern score of patients with SIH.Third, because our center has not yet conducted DSM, conven- tional invasive myelography was used to confirm a CSF leak.But this method cannot diagnose patients with CSF-venous fistula (Dobrocky